Reaction Steps
(1R,2S,7R,8S)-5-(7-Aminomethyl-1,1-dioxo-1,4-dihydro-1λ6-benzo[1,2,4]thiadiazin-3-yl)-3-(4-fluoro-benzyl)-6-hydroxy-3-aza-tricyclo[6.2.1.02,7]undec-5-en-4-one hydrochloride (crude from previous step, ˜0.77 mmol) was dissolved in methylene chloride (10 mL). Triethylamine (2 mL) and pyridine (2 mL) were added. Methane sulfonyl chloride (2 mL) was added and the mixture stirred at 25° C. for 20 min. Water (50 mL) was added and the mixture stirred for 5 min. The solution was diluted with ethyl acetate (200 mL) and washed with 1.0 M aqueous hydrochloric acid solution (3×300 mL), saturated aqueous ammonium chloride solution (2×200 mL) and saturated aqueous brine solution (200 mL). The organic phase was dried over magnesium sulfate, filtered and concentrated in vacuo to afford a clear oil. Purification by flash column chromatography (Teledyne Isco RediSep column; 25-100% ethyl acetate in hexanes) followed by concentration in vacuo afforded the desired product, N-{3-[(1R,2S,7R,8S)-3-(4-fluoro-benzyl)-6-hydroxy-4-oxo-3-aza-tricyclo[6.2.1.02,7]undec-5-en-5-yl]-1,1-dioxo-1,4-dihydro-1λ6-benzo[1,2,4]thiadiazin-7-ylmethyl}-methanesulfonamide (0.139 g, 0.238 mmol, 31%) as a white, brittle foam. 1H NMR (400 MHz, DMSO-d6) δ: 1.19-1.25 (1H, m), 1.40-1.64 (5H, m), 2.50-2.54 (1H, m), 2.64 (1H, d, J=2.5 Hz), 2.92 (3H, s), 3.04 (1H, d, J=8.8 Hz), 3.53 (1H, d, J=9.5 Hz), 4.25 (2H, d, J=6.2 Hz), 4.42 (1H, d, J=15.8 Hz), 4.97 (1H, d, J=14.7 Hz), 7.12-7.17 (2H, m), 7.33 (2H, dd, J1=7.7 Hz, J2=5.4 Hz), 7.52 (1H, d, J=8.7 Hz), 7.63-7.70 (2H, m), 7.81 (1H, s). LC-MS (ESI) calculated for C26H27FN4O6S2 574.14. found 575.3 [M+H+].
